Previous work from this laboratory has demonstrated that when compared to the young adult rat myocardium, that from aged rats exhibits a diminished inotropic response to catecholamines. In addition, the response to these agents in both the canine model and in man is diminished in senescence, compared to that observed in mature adults. The present work includes measurements of cyclic nucleotide levels, and protein kinase activation in perfused rat interventricular septa which have been stimulated with isoproterenol and dibutyryl cAMP, and in which the mechanical response to these agents has been quantitated. Beta receptor number and affinity as well as cAMP-protein kinase stimulation of Ca ion accumulation in isolated sarcoplasmic reticulum have also been measured.